Centrifuge instruments are in common use in research and industrial applications to subject samples to centrifugal force, thereby separating sample components by sedimentation properties. The liquid sample is placed in a container and placed in or attached to a centrifuge rotor. The centrifuge rotor is then rotated by the centrifuge instrument to effect a separation of the components of the liquid sample.
Containers of various sizes and shapes may need to be used in a separation procedure. A rotor for a centrifuge is commonly constructed to hold sample containers having a different diameter or shape than the containers that are actually used to hold a sample. To allow use of a variety of containers, adapters are commonly used with the centrifuge rotor. Such adapters are commonly constructed of a polymeric material but not limited to and constructed as a single piece having a shape which allows retention of one or more containers in which a sample may be placed. The adapter is inserted into a device mounted on or in a centrifuge rotor. The labware holding the sample is inserted in the adapter.
For example, U.S. Pat. No. 6,387,030 discloses an adapter for centrifuge containers having an open top, an interior surface and an exterior surface. The exterior surface of the adapter conforms to the bottom of a cavity in a centrifuge rotor device, such as a swinging bucket held by a rotor. The interior surface of the sample container has an internal sidewall and a bottom having a well to hold a pellet of denser material which has migrated under a centrifugal force. The pellet well extends radially outward from the center of rotation when the adapter is used with a swinging bucket rotor. This configuration allows the pellet to be confined to a localized area resulting in allowing a more compact pellet which remains intact as the adapter is extracted from the centrifuge rotor.
In designing of centrifuge adapters, one issue of concern is preventing agitation of the sample following a centrifuge procedure. Agitation of the sample may cause particulate or denser sample component to become mixed with less dense liquids. For example, U.S. Pat. No. 4,832,678 discloses a tube adapter for centrifuge rotor which includes a plurality of recessed grooves at the top of the adapter to allow engagement of a prong of a removal tool to extract the adapter from the recess of the rotor. Such a system allows an adapter to be extracted even if the adapter sticks somewhat to the recess of a body of a centrifuge rotor. However the disadvantage of using such an extraction system is substantial resuspension of the separated sample material.
The body of a centrifuge rotor is most commonly made of a metal alloy. The adapters are often made of an elastomeric or polymeric material. Such resilient plastic may stick against the surface of the rotor requiring some force in extraction. This is compounded by the centrifugal force of rotation which exerts pressure on the adapter into the rotor body. In addition to spilled or condensed liquids, close tolerances may seal the adapter into a receiving receptacle, creating a vacuum which is difficult to break.
To allow better integrity of a sample following centrifuge rotation, a number of split body tube adapters have been devised. For example, U.S. Pat. No. 4,692,137 discloses a split body adapter which may be hinged at a seam. When the two sections of the adapter are brought into opposing alignment, a recess within the adapter body forms a cavity for receiving a centrifuge tube. These two recessed sections may be substantially identical. During the application of centrifugal force, the behavior of the adapter and the sample container may differ since the adapter is usually made of a different material than the sample container. In many cases the tube deforms into the interior cavity of the adapter. Following the deceleration of the centrifuge rotor, the sample container must be removed from the adapter for subsequent processing and analysis of the sample within the sample container. The described adapter allows the sample container to be removed with reduced force. This allows integrity of the separated sample to be maintained. U.S. Pat. Nos. 5,295,943, 5,399,144, and 5,382,220 disclose a family of related adapters having a pair of hinged adapter body parts which are closed over all or part of a sample container. Another adapter configuration is disclosed in U.S. Pat. No. 5,236,409 in which a sample container is inserted into a centrally cylindrical recess in a tube adapter. A clamp on the bottom of the adapter extends over a second piece of a top inserted over the centrifuge container. This forms a single adapter unit which may subsequently be subjected to centrifugal forces. U.S. Pat. No. 5,935,052 discloses an adapter for fixed angle centrifuge rotor including a pair of adapter sections, which are pressed together to form a unitary structure surrounding a sample container.
While the above adapters have provided a number of alternatives for use with centrifuge rotors and subjecting sample containers to centrifugal forces, some problems remain. For a number of sample containers, it remains difficult to extract sample containers from the adapter, and the adapter from a centrifuge rotor, and such extraction may agitate the sample, thus reducing the separation efficiency.
Additional concerns exist for centrifuge separation using more fragile sample containers that are in common use. One example of such containers are cell culture flasks (also referred to as tissue culture flasks). Cell culture flasks are commonly made of polystyrene or some other similar material. Cell culture flasks generally have a rectangular cross section. This allows efficient stacking of the flasks on incubators for incubation of cell cultures. Such flasks generally are comprised of two or more parts attached at a seam by ultrasonic welding or similar attachment means. Large numbers of such flasks are presently used for a number of different cell culture processes, including culture of adherent cells and suspension cell culture. The current use of such cell culture flasks for the growth of cell cultures does not subject the flask to vacuum or any pressures beyond ambient pressure. (1 g=1 times the force of gravity)
It would be advantageous to be able to harvest cells within cell culture flasks. Common protocols currently require that cells grown in tissue culture flasks be subsequently transferred to an alternative container, such a conical tube, prior to subjecting cells to harvesting by centrifugal force. The cells may then be separated from the surrounding media which would be decanted or aspirated to remove this liquid. The cells may then be resuspended in a new media and subsequently regrown. These procedures have a number of drawbacks. First, a large number of sample containers must be used in each transfer step with attendant cost of labware and disposal of used labware. Second, an experimentalist's time is required for each transfer step. Third, each transfer step from a flask to a centrifuge container (such as a conical tube) has the risk of contaminating cell lines. Such cell lines may be rare and expensive and represent many hours of preparation effort. Finally, the transfer of cells from the cell culture flask may result in loss of cells and possibly degradation of cell lines. Given the time and expense of preparation of such cell lines, minimization of transfer steps would be beneficial.
It is an object of the invention to provide a centrifuge container adapter which facilitates removal of the adapter from the rotor with minimal mixing of separated sample. It is a further object that such an adapter be lightweight. It is a further object of the invention to provide an adapter which is adaptable to use with cell culture flasks. Such an adapter would maintain of the integrity of these flasks while still allowing efficient separation.